Mechanisms for albumin-mediated membrane damage.
1. Bee venom phospholipase A2 causes a small increase in the sublytic leakiness of rabbit erythrocytes which is strongly inhibited by lysolecithin and potentiated by albumin. 2. Albumin extracts long-chain fatty acids from the erythrocyte membrane by a process which is faster than diffusion-determined efflux of fatty acid and during the process it greatly increases the sublytic leakiness of the membrane. In contrast, albumin rapidly terminates sublytic responses to lysolecithin. 3. These actions of albumin are abolished only when albumin is preloaded with four molecules of oleic acid per protein molecule. 4. A minor proportion of the response of phospholipase-A2-treated cells to albumin is due to accumulated fatty acid products; the combination of active enzyme and accumulated fatty acids is much more effective than either alone. Membrane partially depleted of phospholipids by enzyme attack is not highly leaky. 5. Albumin may, in part, act by removing lysolecithin, the inhibitory reaction product. A model is proposed in which susceptibility to phospholipase A2 attack is not uniform on the cell surface and is used to explain the inhibitory action of lysolecithin and the high sensitivity of the membrane in the presence of albumin to damage by newly released fatty acids.
D000818:Animals; D001514:Bee Venoms / Q000494:pharmacology*; D004492:Edetic Acid / Q000494:pharmacology; D004573:Electrolytes / Q000097:blood; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000648:ultrastructure*; D004912:Erythrocytes / Q000648:ultrastructure*; D005227:Fatty Acids / Q000494:pharmacology*; D007700:Kinetics; D009829:Oleic Acids / Q000494:pharmacology; D010741:Phospholipases A / Q000494:pharmacology; D054467:Phospholipases A2; D011817:Rabbits; D012710:Serum Albumin, Bovine / Q000494:pharmacology*
D001514:Bee Venoms; D004573:Electrolytes; D005227:Fatty Acids; D009829:Oleic Acids; D012710:Serum Albumin, Bovine; D004492:Edetic Acid; D010741:Phospholipases A; D054467:Phospholipases A2